Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes.
ABSTRACT Apolipoprotein M plays an important role in the formation of prebeta-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.
The study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.
SNP T-778C was strongly associated with T1D in both Han Chinese (p=0.002, OR=2.188, CI 95%=1.338-3.581) and Swedish (p=0.021, OR=2.865, CI 95%=1.128-7.278) populations. The luciferase activity of -778C promoter was 1.41 times as high as that of -778T promoter (9.90+/-1.92 vs. 7.04+/-0.76, p=0.001).
Allele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.
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ABSTRACT: Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.Experimental and Molecular Medicine 08/2011; 43(11):613-21. · 2.57 Impact Factor
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ABSTRACT: The apolipoprotein M (ApoM) gene is critical in the formation of pre-β-high-density lipoprotein (HDL) and cholesterol efflux to HDL. In this case and control study, 314 ischemic stroke patients and 389 healthy controls were analyzed for three ApoM gene single-nucleotide polymorphisms (SNPs), i.e., C-1065A, T-855C, and T-778C, using a SNaPshot Multiplex sequencing assay. The genotype and allele frequencies of the T-855C were similar in both ischemic stroke patients and the controls. But the frequency of the TC genotype, the C allele of T-778C, and the A allele of the C-1065A SNPs in ischemic stroke patients was significantly higher than that of the healthy controls. After adjusting for confounding risk factors (such as hypertension, diabetes, tobacco smoking, and alcohol consumption), the ApoM gene TC genotype, C allele of T-778C, and A allele of C-1065A were associated with a risk of ischemic stroke. Moreover, plasma levels of total cholesterol were significantly higher in patients with CC or CT genotypes of T-778C than those with TT genotype in the controls. The current data demonstrated that ApoM T-778 C and C-1065A SNPs were associated with increased risk of ischemic stroke in this Han Chinese population.Journal of Molecular Neuroscience 03/2011; 43(3):370-5. · 2.89 Impact Factor
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ABSTRACT: OBJECTIVE: To examine whether the apolipoprotein M (APOM) rs805297 G/T polymorphism is associated with risk of rheumatoid arthritis (RA) in a Chinese population. METHODS: We studied APOM rs805297 G/T gene polymorphism in 520 RA patients, and 520 controls in a Chinese population. Genotyping was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The blood plasma concentration of APOM was measured by an enzyme-linked immunosorbent assay in 84 RA patients and 84 controls. RESULTS: When the APOM rs805297 G/T GG homozygote genotype was used as the reference group, the TT or GT/TT genotype was associated with an increased risk for RA (TT vs. GG, adjusted odds ratio 1.76, 95% CI 1.11-2.77, P=0.016; GT + TT vs. GG, adjusted odds ratio 1.30, 95% CI 1.02-1.67, P=0.037). The average concentration of APOM in plasma was significantly higher in RA patients compared to controls. Stratification analysis found a significantly increased risk for RA associated with the APOM rs805297 TT genotype among male patients, C-reactive protein (CRP)-positive patients, anticitrullinated protein/peptide antibodies (ACPA) - positive patients, rheumatoid factor (RF) - positive patients, patients with higher levels of the erythrocyte sedimentation rate (ESR), patients with higher DAS28 score and patients with higher functional class compared to the APOM rs805297 GG genotype. CONCLUSION: These findings suggest that the functional single-nucleotide polymorphism APOM rs805297 G/T variant allele was associated with RA risk.Joint, bone, spine: revue du rhumatisme 05/2013; · 2.25 Impact Factor